This work continues to explore the utility of mechanism-base inhibitors against enzymes critical for cancer chemotherapy. Successful inhibitors of inosine monophosphate dehydrogenase have been developed and future in vivo studies will be scheduled as soon as larger quantities of drugs become available. Several phosphonate nucleosides were synthesized as possible inhibitors of purine nucleoside phosphorylase but the compounds were inactive. A phosphonate-containing 2',5'-oligoadenylate trimer is being prepared as an enzymatically stable interferon inducer. A project to prepare protein kinase C inhibitors containing a rigid glycerol backbone has been initiated. The work is intended to define the critical spatial relationships which exist between the polar and non-polar groups in known activators of this enzyme.